1. Field of the Invention
This invention relates to the field of medicine, and more particularly to pharmaceutical compositions and methods for the treatment and prevention of respiratory failure.
2. Description of the Related Art
Living things derive their energy from their surroundings. They remove from their environment substances rich in nutrients or energy, degrading them in the process, and rejecting the remains of the degradation process. Respiration is essential for life. The cells of our body consume oxygen (O2) and emit carbon dioxide (CO2). The respiratory system is responsible for carrying out the gaseous exchange between the organism (the blood) and the surrounding atmosphere. The blood transports the gas between the respiratory system and the cells.
The respiratory system is comprised of two principal elements: a respiratory pump (ribcage, respiratory muscle) intended, like bellows, to take in and let out air from the lungs; and a gas diffuser (airways, lungs) which, on an air cell level, performs the O2—CO2 exchange between the blood and the alveolar air.
Respiratory failure is defined as the incapacity of the respiratory system to perform its role, that is to say to maintain normal hematose (transformation of venous blood, rich in CO2, to arterial blood, rich in O2). It can be chronic (slow onset) or acute (sudden onset).
Respiratory failure can have different causes. There are three known major categories of respiratory failure: obstructive syndromes (bronchitis, asthma, cystic fibrosis, etc.); restrictive syndromes (neuromuscular ailments, scolioses, motor disability, excess weight, etc.); and mixed syndromes.
Currently, curative treatment for respiratory failure, besides the treatment of obstructive syndromes by bronchodilators, calls primarily upon mechanical breathing equipment and/or on the supply of oxygen in the case of substantial bronchiole congestion.
All of the proposed solutions therefore refer to processes aimed at increasing the oxygen supply to the body. For example, Japanese Pat. Appl. Publ. No. JP 11-29410 published on Feb. 2, 1999 describes the use of DHA phospholipids for administration in the form of an aerosol, in the treatment of lung disease during acute attacks. The described treatment is not suitable for the long term and is aimed only at improving the oxygen supply to the body in the short term.
Another of the processes described in the art, is aimed at improving the oxygen uptake and its transport in the body by the blood, particularly in the long term.
Currently, no medicine exists which is aimed specifically at the symptomatic prevention of respiratory failure in humans, with proven effectiveness and harmlessness.
It is known that long-chain n-3 fatty acids (n-3 LC-PUFA) such as eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) have multiple effects on cell membranes, in particular, the fluidity of the red corpuscle membranes, and that they are equally likely to act on the vascular contractability and the cardiac rhythm. Thus, the oxygen supply to the body depends on the hemoviscosity, which is linked to the deformability, of the red corpuscles, and on the vasodilatation of the vessels which regulate the peripheral micro-circulation.
The n-3 LC-PUFA are therefore potential agents capable of modulating the oxygenation of tissues and, therefore, of respiration.
It has thus been shown that a daily intake of 3 g of n-3 LC-PUFA (1.8 g of EPA and 1.2 g of DHA) in the form of fish oil, that is to say a dose much higher than the maximum limit of 2 g/day of n-3 LC-PUFA recommended by the AFSSA (Agence Française pour la Sécurité Sanitaire des Aliments˜French Food Standards Agency), leads to an improvement in the maximum respiratory capacity (VO2max) of sportsmen solely after significant endurance exertion (80 min at 70% of their VO2max). But in the absence of long-lasting physical exertion, taking 3 g/day n-3 LC-PUFA had no effect (Léger C L et al. Cah. Nutr. Diét, XXVII, 2, 1992). This has been confirmed elsewhere; Mickleborough T D et al., Am. J. Respir. Crit. Care Med. 168 (10), 1181-9 (2003) have shown that the daily intake of 3.2 g of EPA and 2.2 g of DHA in the form of fish oil had no effect on the pulmonary function before exertion of elite athletes.